Initiation and maintenance of latent herpes simplex virus infections: the paradox of perpetual immobility and continuous movement.

During the acute phase of infection, herpes simplex virus (HSV) is taken up by nerve endings and travels, probably as a noninfectious nucleocapsid, toward the neurons of sensory ganglia. Infectious virus can be detected in ganglia for a limited period, after which the virus enters into a latent phase. It appears that synthesis of deoxyribonucleic acid is not required and that an early viral protein and at least one additional late virus gene product are involved in the establishment of latency. The distinction between a "static" and a "dynamic" form of latency depends on the ability to detect viral activities in neurons and on whether these observed activities are expressed continuously or intermittently. The development of recurrent lesions following virus reactivation is an occasional event and is controlled by inducing agents and the state of the organism. The maintenance of latency depends on the number of neurons that become latently infected after the primary episode, the number of neurons in which reactivation takes place, the fate of the neuron after virus reactivation, and the possibility of renewed neuronal infections after each recurrent episode. Exogenous reinfections may also contribute to the maintenance of latency since they can lead to latent infections in nearby or distantly located sensory ganglia. Multiple latent infections may result also from a single primary infection by dissemination of the virus to distantly located ganglia.